News & Publications

GMET NEWS
SELECTED PUBLICATIONS

Following are selected peer-reviewed publications with General Metabolics founders and advisors.

Metabolomics Identifies a Biomarker Revealing in Vivo Loss of Functional ß-Cell Mass Before Diabetes Onset.

Diabetes, 2019

Regulatory mechanisms underlying coordination of amino acid and glucose catabolism in E. coli.

Nature Communications, 2019

Antibodies set boundaries limiting microbial metabolite penetration and the resultant mammalian host response.

Immunity, 2018

Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity.

Cell, 2018

Synthesis and degradation of FtsZ quantitatively predicts the first cell division in starved bacteria.

Molecular Systems Biology, 2018

High-throughput dynamic metabolomics identifies mode of action for uncharacterized antimicrobial compounds.

Science Translational Medicine, 2018

Genomewide landscape of gene–metabolome associations in Escherichia coli.

Molecular Systems Biology, 2017

Nontargeted in vitro metabolomics for high-throughput identification of novel enzymes in Escherichia coli.

Nature Methods, 2017

Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity.

Cell Metabolism, 2017

Metabolic control of TH17 and induced Treg cell balance by an epigenetic mechanism.

Nature, 2017

L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity.

Cell, 2016

GAM: a web-service for integrated transcriptional and metabolic network analysis.

Nucleic Acids Research, 2016

Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization.

Immunity, 2015

High-Throughput, Accurate Mass Metabolome Profiling of Cellular Extracts by Flow Injection time-of-Flight Mass Spectrometry.

Analytical Chemistry, 2011

APPLICATION SPOTLIGHT

Following are summaries of recent publications by our clients and collaborators that highlight applications of our technology

Ulland et al. use high-throughput metabolomics to identify metabolic pathways implicated in Alzheimer's Disease

(C) 2017 Elsevier Inc.

Alzheimer’s Disease is a debilitating neurodegenerative illness for which there are currently no effective treatments. Mutations in the AD-associated gene TREM2 have been implicated in dysregulated microglial autophagy – the degradation of intracellular structures in immune cells that regulate homeostasis in the central nervous system.

In this study, Ulland et al. harnessed the broad coverage of General Metabolics’ high-throughput untargeted metabolomics platform to identify statistically significant differences in metabolite abundances associated with multiple biochemical pathways in TREM2-deficient immune cells. Network-based integration of metabolomics and RNA-seq data revealed differential regulation of diverse metabolic pathways including nucleotide biosynthesis, protein glycosylation, phospholipid metabolism, as well as glycolysis, TCA cycle, and amino acid degradation.

These findings prompted further targeted analyses of cellular energetics and oxygen consumption rates. The observation that energy utilization was impaired in TREM2-deficient immune cells lead the authors to test whether the addition of cyclocreatine, a bioavailable creatine-phosphate precursor, could increase microglial energy levels and decrease autophagy in TREM2-deficient mice. Additional biochemical assays confirmed that dietary cyclocreatine supplementation was sufficient to improve microglial metabolism and reduced plaque-associated neurite dystrophy, a hallmark of Alzheimer’s Disease.

These findings add to a growing body of evidence that highlights the important role that cellular metabolic regulation plays in maintaining homeostasis in the tissues of the central nervous system, as well as the utility of untargeted omics technologies for generating specific biological hypotheses.

If you would like to learn more about how our high-throughput untargeted metabolomics platform can support your research, please contact us.